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Annual Review of Immunology

Volume 43, 2025

Cellular and Molecular Mechanisms of Innate Memory Responses

  • Musa M. Mhlanga1,2,3, Stephanie Fanucchi4, Mumin Ozturk1,2 and Maziar Divangahi5,6
  • 1Epigenomics & Single Cell Biophysics Group, Department of Cell Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University, Nijmegen, The Netherlands; email: [email protected] 2Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands 3Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands 4Lemba Therapeutics, Nijmegen, The Netherlands 5Departments of Medicine, Pathology, and Microbiology & Immunology, McGill University, Montreal, Quebec, Canada 6McGill University Health Centre, McGill International TB Centre, and Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada; email: [email protected]
  • Vol. 43:615-640 (Volume publication date April 2025)
  • Copyright © 2025 by the author(s).
    This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See credit lines of images or other third-party material in this article for license information.

Abstract

There has been an increasing effort to understand the memory responses of a complex interplay among innate, adaptive, and structural cells in peripheral organs and bone marrow. Trained immunity is coined as the de facto memory of innate immune cells and their progenitors. These cells acquire epigenetic modifications and shift their metabolism to equip an imprinted signature to a persistent fast-responsive functional state. Recent studies highlight the contribution of noncoding RNAs and modulation of chromatin structures in establishing this epigenetic readiness for potential immune perturbations. In this review, we discuss recent studies that highlight trained immunity–mediated memory responses emerging intrinsically in innate immune cells and as a complex interplay with other cells at the organ level. Lastly, we survey epigenetic contributors to trained immunity phenotypes—specifically, a recently discovered regulatory circuit coordinating the regulation of a key driver of trained immunity.

Keyword(s): epigenetics, immunometabolism, innate immunity, noncoding RNA, organ-trained immunity, vaccine immunology
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2025-04-25
2025-06-19
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Cellular and Molecular Mechanisms of Innate Memory Responses
Annual Review of Immunology 43, 615 (2025); https://doi.org/10.1146/annurev-immunol-101721-035114
/content/journals/10.1146/annurev-immunol-101721-035114
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